P-BCMA-101 Tscm CAR-T Cells in the Treatment of Patients With Multiple Myeloma (MM)

Phase 2TerminatedNCT03288493

Poseida Therapeutics, Inc.105 enrolled

Overview

Phase 1 of the study is comprised of an open-label, single ascending dose (SAD), multiple cohort study; a multiple dose cycle administration cohort study; and a combination administration study of P-BCMA-101 autologous T stem cell memory (Tscm) CAR-T cells in patients with relapsed / refractory MM. Followed by a Phase 2, open-label, efficacy and safety study. Rimiducid may be administered as indicated.

Phase 1 follows a 3 + 3 design of dose-escalating cohorts. Phase 2 of the study is an open-label multi-center efficacy and safety study. After a patient enrolls, leukapheresis will be performed to obtain peripheral blood mononuclear cells which will be sent to a manufacturing site to produce P-BCMA-101 CAR-T cells. The cells will then be returned to the investigational site and, after a standard chemotherapy based conditioning regimen, will be administered to the patient across 1-3 infusions, with or without combination therapy. Treated patients will undergo serial measurements of safety, tolerability and response. Rimiducid may be administered as indicated.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

105

Conditions

Multiple Myeloma

Interventions

P-BCMA-101 CAR-T cellsBIOLOGICAL

P-BCMA-101 is an autologous, principally Tscm, CAR-T cell product (also called called a CARTyrin T cell product) targeting the myeloma selective protein BCMA. P-BCMA-101 cells are produced using a non-viral vector carrying the gene for an anti-BCMA Centyrin-based (small, fully human binding domain, designed to increase T cell persistence and decrease exhaustion) chimeric antigen receptor (CAR). Secondary to the large carrying capacity of the non-viral vector, P-BCMA-101 cells carry two additional genes, a selection gene used to manufacture a purified product and a "safety switch" gene to allow the cells to be eliminated if desired. Rimiducid (safety switch activator) may be administered as indicated.

RimiducidDRUG

Rimiducid (safety switch activator) may be administered as indicated.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Males or females, ≥18 years of age * Must have a confirmed diagnosis of active MM * Must have measurable MM * Must have relapsed / refractory MM, having received treatment with proteasome inhibitor and IMiD \[Phase 2: Must have relapsed / refractory MM, and refractory to last line of therapy, having received treatment with proteasome inhibitor, an IMiD, CD38 targeted therapy and undergone autologous stem cell transplant (ASCT) or not a candidate for ASCT.\] * Must have adequate hepatic, renal, cardiac and hematopoietic function Exclusion Criteria: * Is pregnant or lactating * Has inadequate venous access and/or contraindications to leukapheresis * Has active hemolytic anemia, plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome, disseminated intravascular coagulation, leukostasis, amyloidosis, significant autoimmune, CNS or other malignant disease * Has an active second malignancy (not disease-free for at least 5 years) in addition to MM, excluding low-risk neoplasms such as non-metastatic basal cell or squamous cell skin carcinoma. * Has active autoimmune disease * Has a history of significant central nervous system (CNS) disease, such as stroke, epilepsy, etc. * Has an active systemic infection * Has hepatitis B or C virus, human immunodeficiency virus (HIV), or human T-lymphotropic virus (HTLV) infection, or any immunodeficiency syndrome. * Has any psychiatric or medical disorder that would preclude safe participation in and/or adherence to the protocol * Has receiving immunosuppressive or other contraindicated therapies within the excluded time frame from entry * Has CNS metastases or symptomatic CNS involvement * Has a history of having undergone allogeneic stem cell transplantation, or any other allogeneic or xenogeneic transplant, or has undergone autologous transplantation within 90 days. * Unable to take acetylsalicylic acid (ASA) daily as prophylactic anticoagulation. (Cohorts R and RP only). * History of thromboembolic disease within the past 6 months, regardless of anticoagulation (Cohorts R and RP only).

Locations (16)

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

University of California Davis

Davis, California, United States

Outcomes

Primary Outcomes

Phase 1: Assess the Safety of P-BCMA-101

Incidence and severity of treatment-emergent adverse events

Time frame: Baseline through Day 28

Phase 1: Maximum Tolerated Dose of P-BCMA-101

Rate of dose limiting toxicities (DLT)

Time frame: Baseline through Day 28

Phase 2: Assess the Safety of P-BCMA-101

Incidence and severity of treatment-emergent adverse events

Time frame: Baseline through 24 months

Phase 2: Assess the Efficacy of P-BCMA-101 (ORR)

According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma: Overall Response Rate (ORR)-Percentage of patients with complete response (CR), very good partial response (VGPR), or partial response (PR).

Time frame: Baseline through 24 months

Phase 2: Assess the Efficacy of P-BCMA-101 (DOR)

According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma: Duration of Response (DOR)-Time from complete response (CR), very good partial response (VGPR), or partial response (PR) to progressive disease.

Time frame: Baseline through 24 months

Secondary Outcomes

Phase 1:Assess the Safety of P-BCMA-101

Incidence and severity of treatment-emergent adverse events

Time frame: Baseline through Month 24

Phase 1:Assess the Feasibility P-BCMA-101

Ability to generate protocol-prescribed doses of P-BCMA-101.

Data from ClinicalTrials.gov

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